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Updated: Nov 10, 2025
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Directly Measuring Forces Within Reconstituted Active Microtubule Bundles
Published on: May 10, 2022
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A cytoskeletal function for PBRM1 reading methylated microtubules.
Menuka Karki1, Rahul K Jangid1, Ramakrishnan Anish2
1Center for Precision Environmental Health, Baylor College of Medicine, Houston, TX 77030, USA.
Science Advances
|April 3, 2021
Summary
The epigenetic machinery coordinates genome and cytoskeleton functions. PBRM1 reads microtubule marks, ensuring normal mitosis and genomic stability, revealing new disease mechanisms.
Area of Science:
- Molecular Biology
- Cell Biology
- Epigenetics
Background:
- Epigenetic effectors regulate genome function by reading and writing chromatin marks.
- The interplay between epigenetic machinery and cellular structures like the cytoskeleton is not fully understood.
Purpose of the Study:
- To investigate the role of the PBAF chromatin remodeling complex, specifically PBRM1, in cytoskeletal regulation.
- To elucidate the mechanism by which PBRM1 interacts with epigenetic marks on the cytoskeleton.
Main Methods:
- Investigated the interaction between PBRM1 and methyl marks on microtubules.
- Utilized SETD2 methyltransferase and PBRM1 BAH domains in experiments.
- Assessed the impact of disrupted interactions on mitosis and genomic stability.
Main Results:
- PBRM1 binds to SETD2-written methyl marks on microtubules via its BAH domains.
- This binding recruits PBAF components to the mitotic spindle, essential for normal mitosis.
- Loss of SETD2 methylation or mutations in PBRM1's BAH domains disrupt this process, leading to genomic instability.
Conclusions:
- PBRM1 integrates chromatin and cytoskeletal activity through its distinct binding domains.
- Coordinated epigenetic machinery activity on the cytoskeleton is conserved.
- Defects in chromatin remodelers can cause disease through combined epigenetic and cytoskeletal dysfunction.
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